Protection against reperfusion injury by 3′,4′-dihydroxyflavonol in rat isolated hearts involves inhibition of phospholamban and JNK2

Chin, Kai Yee; Silva, Lokugan S.; Darby, Ian A.; Ng, Dominic C. H.; Woodman, Owen L.

doi:10.1016/j.ijcard.2017.11.101

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…There is plenty of evidence showing that DOX-induced cardiotoxicity includes ROS production, mitochondrial dysfunction, and apoptosis (Dhalla et al, 2000; Green and Leeuwenburgh, 2002; Pereira et al, 2011). It has been established by several studies in different animal models that DiOHF has cardioprotective effects against myocardial ischemia–reperfusion injury (Wang et al, 2004; Qin et al, 2011; Woodman et al, 2014; Thomas et al, 2015; Chin et al, 2018). Similar to the cardiac ischemia–reperfusion injury, oxidative stress and cardiomyocyte apoptosis are also mediators for the DOX-induced cardiotoxicity (Dhalla et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

DiOHF Protects Against Doxorubicin-Induced Cardiotoxicity Through ERK1 Signaling Pathway

Chang

Cheng

et al. 2019

Front. Pharmacol.

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Doxorubicin (DOX) is an effective anticancer agent. Its clinical use is, however, limited due to its detrimental side effects, especially the cardiotoxicity caused by ROS, mitochondrial dysfunction and apoptosis. 3’,4’-dihydroxyflavonol (DiOHF) is a recently developed potent synthetic flavonoid which has been reported to exert anti-oxidative activity in myocardial ischemia–reperfusion injury and maintain the normal mitochondrial function. The aim of this study was to explore the protective effects of DiOHF on the DOX-induced cardiotoxicity. We established DOX-induced cardiotoxicity in H9C2 cells by incubation with 1 μM DOX and in BALB/c mice by DOX injection. DiOHF effectively prevented and reversed the DOX-induced cardiotoxicity, including ROS production, mitochondrial dysfunction, and apoptosis. The DOX-induced cardiotoxicity was accompanied by ERK1/2 activation and abolished by the silence of ERK1, rather than ERK2. Furthermore, DOX treatment in mice induced an increase in serum CK-MB level and myocardial fibrosis with a reduction in left ventricular (LV) function. These detrimental effects were blunted by DiOHF administration. Conclusion: DiOHF suppresses and reverses the DOX-induced cardiotoxicity by inhibiting ROS release, stabilizing mitochondrial function and reducing apoptosis through activation of the ERK1 signaling.

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Section: Discussionmentioning

confidence: 99%

DiOHF Protects Against Doxorubicin-Induced Cardiotoxicity Through ERK1 Signaling Pathway

Chang

Cheng

et al. 2019

Front. Pharmacol.

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“…Now, Woodman and co-workers report that antioxidant flavonol can mitigate reperfusion injury via regulating the signaling pathway involved in inhibition of phospholamban (PLN) and JNK2 (4). Cytosolic calcium overload during early reperfusion contributes to calcium oscillation and eventual uncoordinated contracture, MPTP opening, and eventual cell death.…”

Section: Signaling Involved In Srmentioning

confidence: 99%

Comparing cardioprotetion by DiOHF intervention and ischemic preconditioning

Chen

2018

International Journal of Cardiology

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“…Flavanone, an important natural compound, has great potential to reduce the risk of mortality in patients with cardiovascular diseases (1)(2)(3). Flavanone is widely distributed in plants, fruits and vegetables, and consists of a large group of naturally existing polyphenolic compounds (4).…”

Section: Introductionmentioning

confidence: 99%

Structure‑activity associations in novel farrerol derivatives with vasorelaxant properties

2018

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To detect the structure‑activity associations of farrerol derivatives, the relaxation activity of farrerol derivatives was observed in isolated aortic rings pre‑contracted using phenylephrine in Sprague‑Dawley rats. All compounds tested in the present study produced a relaxation effect, which was significantly affected by the molecular structure. Using a collagen gel contraction assay, the present study further evaluated the inhibitiory effect of farrerol derivatives in a decreased collagen gel area, induced by Angiotensin II. The results indicated that farrerol derivatives could inhibit collagen contraction, and that the inhibitory effect was associated with the molecular structure of the compounds. Furthermore, the inhibitory strength of the different compounds was consistent with the results of vascular tension detection. The activity of the farrerol derivatives was closely associated with the molecular structure. The analysis indicated that an electron‑withdrawing substituent in the ortho position of the phenyl group (ring B) was crucial in order to observe improved vasorelaxation activity, whereas a hydroxyl or methoxy group was unfavorable. A para electron‑donating group was oberved to increase compound activity. In addition, when the B ring was heterocycle rather than a phenyl ring, the vasorelaxation ability was weakened.

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Protection against reperfusion injury by 3′,4′-dihydroxyflavonol in rat isolated hearts involves inhibition of phospholamban and JNK2

Cited by 6 publications

References 43 publications

DiOHF Protects Against Doxorubicin-Induced Cardiotoxicity Through ERK1 Signaling Pathway

DiOHF Protects Against Doxorubicin-Induced Cardiotoxicity Through ERK1 Signaling Pathway

Comparing cardioprotetion by DiOHF intervention and ischemic preconditioning

Structure‑activity associations in novel farrerol derivatives with vasorelaxant properties

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